Methods And Apparatuses Related To Magnetic Relaxometry Measurements In The Presence Of Environmental Response To Magnetic Excitation

ABSTRACT

Example embodiments of the present invention provide a magnetic relaxometry measurement apparatus, comprising: a magnetizing system configured to supply a pulsed magnetic fields to a sample; a sensor system configured to detect magnetic fields produced by induced magnetization of the sample after a magnetic field pulse from the magnetizing system; one or more compensating coils configured to suppress generation of eddy currents in an environment surrounding the apparatus due to the pulsed magnetic fields.

TECHNICAL FIELD

The subject invention relates to the field of magnetic relaxometrymeasurements, specifically the use of extra coils to reduce undesirableeffects of magnetic fields from the environment surrounding themeasurement.

BACKGROUND ART

Measurement of the magnetic relaxation of superparamagneticnanoparticles has been proposed for use in a variety of applications,including several biological and medical applications. See, e.g., patentapplication U.S. Ser. No. 13/870,925; U.S. Ser. No. 13/249,994; U.S.Ser. No. 11/940,673; U.S. Ser. No. 12/337,554; U.S. Ser. No. 11/957,988;PCT/US2010/051417; PCT/US2010/055729; and PCT/US2011/28746; each ofwhich is incorporated herein by reference.

At least two distinct types of environmental influences can affectmeasurements of magnetic relaxation of superparamagnetic nanoparticles.A first influence is environmental noise (including urban noise), whichis not produced by the detection/excitation superparamagnetic relaxation(SPMR) measurement protocol itself. This noise includes contributionsfrom sub-Hz frequencies up to high-order line harmonics. Such noise canbe suppressed by magnetic and RF shielding, which typically involvemagnetically and radio frequency shielded rooms or enclosures. Suchnoise can also be suppressed by active shielding.

A second type of noise is produced by the response of the environment tothe magnetic excitation pulse that is part of the SPMR protocol itself.The present invention provides methods and apparatuses that caneffectively mitigate this type of noise.

SUMMARY OF INVENTION

Example embodiments of the present invention provide a magneticrelaxometry measurement apparatus, comprising: a magnetizing systemconfigured to supply a pulsed magnetic fields to a sample; a sensorsystem configured to detect magnetic fields produced by inducedmagnetization of the sample after a magnetic field pulse from themagnetizing system; one or more compensating coils configured tosuppress generation of eddy currents in an environment surrounding theapparatus due to the pulsed magnetic fields.

In some embodiments, the one or more compensating coils comprise a firstz-axis coil mounted above the magnetizing system and configured tosupply a first z-axis magnetic field oriented generally vertically andcoaxial with a vertical component of the magnetizing system field.

In some embodiments, the one or more compensating coils further comprisea second z-axis coil mounted beneath the magnetizing system andconfigured to supply a second z-axis magnetic field oriented generallyvertically and coaxial with a vertical component of the magnetizingsystem field.

In some embodiments, the one or more compensating coils comprise a firstx-axis coil mounted to one side of the magnetizing system and configuredto supply a first x-axis magnetic field oriented generally horizontallyand orthogonal to a vertical component of the magnetizing system field.

In some embodiments, the one or more compensating coils comprise asecond x-axis coil mounted to one side of the magnetizing system,opposite the first x-axis coil, and configured to supply a second x-axismagnetic field oriented generally horizontally and orthogonal to avertical component of the magnetizing system field.

In some embodiments, the one or more compensating coils comprise a firsty-axis coil mounted to one side of the magnetizing system, 90 degreesfrom the first x-axis coil, and configured to supply a first y-axismagnetic field oriented generally horizontally and orthogonal to avertical component of the magnetizing system field and orthogonal to thefirst x-axis magnetic field.

In some embodiments, the one or more compensating coils comprise asecond y-axis coil mounted to one side of the magnetizing system, 90degrees from the first x-axis coil, and configured to supply a secondy-axis magnetic field oriented generally horizontally and orthogonal toa vertical component of the magnetizing system field and orthogonal tothe first x-axis magnetic field.

In some embodiments, the one or more compensating coils comprise asecond x-axis coil mounted to one side of the magnetizing system,opposite the first x-axis coil, and configured to supply a second x-axismagnetic field oriented generally horizontally and orthogonal to avertical component of the magnetizing system field.

In some embodiments, the magnetizing system is configured to provide amagnetizing pulse sequence comprising an applied magnetization field ofa first magnitude for a first time, and of a second magnitude for asecond time, and wherein the one or more compensating coils areconfigured to provide a compensating pulse sequence comprising a thirdmagnitude for a third time, and of a fourth magnitude for a fourth time.In some embodiments, the third magnitude is up to 50% of the firstmagnitude, and the fourth magnitude is up to 50% of the secondmagnitude. In some embodiments, the second magnitude is zero. In someembodiments, the third time is equal to the first time, and the fourthtime is equal to the second time. In some embodiments, the first time isequal to 0.75 seconds, and the second time is equal to 2.25 seconds. Thethird time can be contemporaneous with the first time, or can bedelayed, for example by 1 to 5 milliseconds. In some embodiments, thesecond time is greater than the first time. In some embodiments, thesecond time is less than the first time. In some embodiments, the thirdmagnitude is up to 50% of the first magnitude, and the fourth magnitudeis up to 50% of the second magnitude.

Example embodiments of the present invention provide a method of makinga magnetic relaxometry measurement, comprising providing an apparatus asdescribed herein, using the magnetizing system to provide magnetizationpulse sequence consisting of a magnetizing field on for a first time andoff for a second time, using the one or more compensating coils toprovide a compensation pulse on for a third time and off for a fourthtime, and using the sensor system to detect a magnetization of thesample during the second time.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic illustration of an example embodiment of thepresent invention.

FIG. 2 is an illustration of measurement performance obtained using anexample embodiment of the present invention.

DESCRIPTION OF EMBODIMENTS AND INDUSTRIAL APPLICABILITY

The present invention can be useful in magnetic relaxometry methods andapparatuses like those described in patent application U.S. Ser. No.13/870,925; U.S. Ser. No. 13/249,994; U.S. Ser. No. 11/940,673; U.S.Ser. No. 12/337,554; U.S. Ser. No. 11/957,988; PCT/US2010/051417;PCT/US2010/055729; and PCT/US2011/28746; each of which is incorporatedherein by reference. Detailed examples of magnetic relaxometry systemsand methods are presented in the referenced patents and applications,and are not repeated herein though the present description relies on theunderstanding of one skilled in the art after examination of thereferenced patents and applications.

An SPMR measurement performed on a sample of superparamagneticnanoparticles generally includes application of a pulsed magnetic fieldB^(M) after which the magnetic Neel relaxation of the nanoparticles isdetected by sensors such as sensitive magnetometers or magneticgradiometers. The field temporal gradient dB^(M)/dt during pulseswitching induces Eddy currents in the surrounding environment which canbe dependent on the size, structure, composition and form of thesurrounding conducting environment, and can persist long enough tocreate a signal in the time or frequency band of the SPMR measurement.The pulsed magnetic field can also cause certain magnetic materials toacquire time varying magnetization or a remnant one.

To address the Eddy currents formation, example embodiments of thepresent invention provide a system as depicted in FIG. 1 for activemagnetic field compensation. The system comprises one or more temporalgradient coils 2 (two coaxial coils are shown in the figure; a singlecoil can be suitable, as can multiple coils disposed on different axes)that act mainly on the conductive environment by compensating theinduced temporal gradient by the main magnetizing coils 1 thus producinga vanishing temporal magnetic field gradient at multiple parts of theconductive environment, as an example at as many parts of the conductiveenvironment as possible. The temporal gradient coils are also referredto as compensating coils herein. It is generally desirable that thetemporal gradient coils 2 not affect the measurement on thesuperparamagnetic nanoparticles sample. The sample containing thenanoparticle can be of any kind—nanoparticle phantoms, tissue, organ,cells, tumors containing nanoparticle, and others.

FIG. 1 is a schematic illustration of a typical magnetorelaxometrymeasurement system for measuring nanoparticles, with the addition oftemporal gradient coils 2. A main magnetizing coil system 1 produces amagnetic field pulse in the positive z-axis direction for themagnetization of the nanoparticle sample 5. The following SPMR of thenanoparticle is measured by magnetic sensor(s) 3. The switching magneticfield from the main magnetizing coil system induces Eddy currents in thesurrounding conductive environment 6 which in turn produces magneticfield also detected by the sensor(s) 3.

The example embodiment provides temporal gradient coils 2 that cansuppress the generation of Eddy currents. The system can be placed incommunication with a power system (not shown in the figure) configuredto supply electrical current to the temporal gradient coils 2 and acontrol system to control the timing and power of the electricalcurrent, in cooperation with control of the rest of themagnetorelaxometry measurement system. The temporal gradient coils 2generate one or more magnetic field pulses with direction (coil systemaxis) at an angle to the B^(M) (depicted in FIG. 1 with an angle of 180degrees, or opposite direction to B^(M)). The magnetic pulse sequence ofthe temporal gradient coils 2 can be adjustable but in general is closeto the B^(M) pulse sequence. The spatial position, the size of the coilsystem, and the strength of the magnetic field and temporal gradient ofthe temporal gradient coils 2 are chosen such that a small (in someapplications a vanishingly small) temporal gradient is created in theconductive environment 7 thus suppressing the transient magnetic signalintroduced in the magnetic sensor 3. Note that the example on FIG. 1shows one side of z-axis compensation of dB^(M)/dt (upper coil 2) but itcan be applied also to the bottom part of coil system 2 as well as tothe x- and y-axes (simultaneous or not) or in general in any desireddirection, depending as examples on the characteristics of theconductive environment. Reducing the magnetic transient signal into thedetector(s) lowers the effective background signal of the SPMRmeasurement on nanoparticle samples thus improving the sensitivity andlower detection level of SPMR Instrument.

The present invention comprises temporal gradient coils as describedherein, magnetic relaxometry systems including temporal gradient coilsas described herein, and methods of operating such systems and methodsof making magnetic relaxometry measurements using such systems.

An example embodiment comprises a Helmholz coil system having first andsecond square coils each having sides of between 50 cm and 70 cm,nominally 60 cm, corresponding to the coils 1 in FIG. 1. The embodimentfurther comprised a single temporal gradient coil of similar size,corresponding to only the upper temporal gradient coil 2 in FIG. 1. Theseparation between the upper of the two Helmholtz coils and the temporalgradient coil was between 4 and 9 feet, for example adjustable between 5and 8 feet. The Helmholtz coil system was configured to produce amagnetic field of 50 Gauss to 70 Gauss, for example 60 Gauss,homogeneous field at its center while the temporal gradient coil wasconfigured to produce a magnetic field of up to 35 Gauss, for example 20Gauss, at its center.

The temporal gradient coil was configured such that the product of thecurrent supplied and the number of turns, and the exact position abovethe Helmholtz system, produced Eddy currents in conductive environmentalcomponents that at least partially counteracted those produced by theHelmholtz system due to pulsing of the field in the Helmholtz coilsystem. The examples given above were suitable for the environmentsurrounding the example embodiment. Other environments, e.g., buildingconstruction style; amount and type of metal embedded in walls, ceiling,and floor; other metal in the room; distances between the coils and thefeatures in the environment; can indicate that different temporalgradient coil configurations, or different magnetization, or both, aredesirable.

In a magnetic relaxometry measurement using the example embodiment, theHelmholtz coil system was operated with up to one second current pulsewith fast switching of the current (less than 2 milliseconds from off tofull current), corresponding to about one second of magnetization fromthe Helmholtz coil system; followed by 2 to 3 seconds of zero currentapplied, corresponding to no magnetization from the Helmholtz coilsystem. Other timing can be suitable, e.g., 0.75 seconds magnetizationfollowed by 2.25 seconds of no magnetization. The temporal gradient coilsystem was operated with a similar pulse timing sequence. The temporalgradient coil system can also be operated with a phase shift or timedelay between the Helmholtz coil system and the temporal gradient coilsystem. The temporal gradient coil system can also be operated withsimilar overall timing but with a shorter current on (magnetization)time for the temporal gradient coil system as compared with that of theHelmholtz coil system.

FIG. 2 illustrates benefits obtained in making magnetic relaxometrymeasurements using the example embodiment. The upper curves 1 in thefigure correspond to measurements made without the temporal gradientcoil in operation, and the lower curves 2 in the figure correspond tomeasurements made with the temporal gradient coil in operation. Thereare seven curves in each portion of the figure; note that some mayoverlap. The curves represent the voltages produced by sevensecond-order SQUID axial gradiometers measuring the magnetic response ofthe environment. Note also that the vertical shift of each channel andnoise are different due to gradiometer positions and different intrinsicbalance of each gradiometer. The minimization of the environmentalrelaxation has led to improvement in the lower limit of detection ofsuperparamagnetic nanoparticles by up to a factor of four.

The present invention has been described as set forth herein in relationto various example embodiments and design considerations. It will beunderstood that the above description is merely illustrative of theapplications of the principles of the present invention, the scope ofwhich is to be determined by the claims viewed in light of thespecification. Other variants and modifications of the invention will beapparent to those of skill in the art.

We claim:
 1. A magnetic relaxometry measurement apparatus, comprising: amagnetizing system configured to supply a pulsed magnetic fields to asample; a sensor system configured to detect magnetic fields produced byinduced magnetization of the sample after a magnetic field pulse fromthe magnetizing system; one or more compensating coils configured tosuppress generation of eddy currents in an environment surrounding theapparatus due to the pulsed magnetic fields.
 2. An apparatus as in claim1, wherein the one or more compensating coils comprise a first z-axiscoil mounted above the magnetizing system and configured to supply afirst z-axis magnetic field oriented generally vertically and coaxialwith a vertical component of the magnetizing system field.
 3. Anapparatus as in claim 2, wherein the one or more compensating coilsfurther comprise a second z-axis coil mounted beneath the magnetizingsystem and configured to supply a second z-axis magnetic field orientedgenerally vertically and coaxial with a vertical component of themagnetizing system field.
 4. An apparatus as in claim 1, wherein the oneor more compensating coils comprise a first x-axis coil mounted to oneside of the magnetizing system and configured to supply a first x-axismagnetic field oriented generally horizontally and orthogonal to avertical component of the magnetizing system field.
 5. An apparatus asin claim 4, wherein the one or more compensating coils comprise a secondx-axis coil mounted to one side of the magnetizing system, opposite thefirst x-axis coil, and configured to supply a second x-axis magneticfield oriented generally horizontally and orthogonal to a verticalcomponent of the magnetizing system field.
 6. An apparatus as in claim4, wherein the one or more compensating coils comprise a first y-axiscoil mounted to one side of the magnetizing system, 90 degrees from thefirst x-axis coil, and configured to supply a first y-axis magneticfield oriented generally horizontally and orthogonal to a verticalcomponent of the magnetizing system field and orthogonal to the firstx-axis magnetic field.
 7. An apparatus as in claim 6, wherein the one ormore compensating coils comprise a second y-axis coil mounted to oneside of the magnetizing system, 90 degrees from the first x-axis coil,and configured to supply a second y-axis magnetic field orientedgenerally horizontally and orthogonal to a vertical component of themagnetizing system field and orthogonal to the first x-axis magneticfield.
 8. An apparatus as in claim 7, wherein the one or morecompensating coils comprise a second x-axis coil mounted to one side ofthe magnetizing system, opposite the first x-axis coil, and configuredto supply a second x-axis magnetic field oriented generally horizontallyand orthogonal to a vertical component of the magnetizing system field.9. An apparatus as in claim 1, wherein the magnetizing system isconfigured to provide a magnetizing pulse sequence comprising an appliedmagnetization field of a first magnitude for a first time, and of asecond magnitude for a second time, and wherein the one or morecompensating coils are configured to provide a compensating pulsesequence comprising a third magnitude for a third time, and of a fourthmagnitude for a fourth time.
 10. An apparatus as in claim 9, wherein thethird magnitude is 50% of the first magnitude, and the fourth magnitudeis 50% of the second magnitude.
 11. An apparatus as in claim 10, whereinthe second magnitude is zero.
 12. An apparatus as in claim 9, whereinthe third time is equal to the first time, and the fourth time is equalto the second time.
 13. An apparatus as in claim 9, wherein the firsttime is equal to 0.75 seconds, and the second time is equal to 2.25seconds.
 14. An apparatus as in claim 9, wherein the second time isgreater than the first time.
 15. An apparatus as in claim 9, wherein thesecond time is less than the first time.
 16. An apparatus as in claim 9,wherein the third magnitude is 50% of the first magnitude, and thefourth magnitude is 50% of the second magnitude.
 17. A method of makinga magnetic relaxometry measurement, comprising providing an apparatus asin claim 1, using the magnetizing system to provide magnetization pulsesequence consisting of a magnetizing field on for a first time and offfor a second time, using the one or more compensating coils to provide acompensation pulse on for a third time and off for a fourth time, andusing the sensor system to detect a magnetization of the sample duringthe second time.